Parkinson's disease phenotype is influenced by the severity of the mutations in the GBA gene

Parkinsonism Relat Disord. 2018 Oct;55:45-49. doi: 10.1016/j.parkreldis.2018.05.009. Epub 2018 May 17.


Objective: Mutations in the glucocerebrosidase (GBA) gene are divided into mild and severe (mGBA, sGBA) based on their contribution to the phenotype of Gaucher disease (GD) among homozygotes. We conducted a longitudinal analysis of Parkinson's disease (PD) patients carrying mutations in the GBA gene to better characterize genotype-phenotype correlations.

Methods: Patients underwent a comprehensive assessment of medical, neurological, cognitive and non-motor functions. Data from these patients was explored to evaluate differences in disease phenotype based on genotype.

Results: A total of 355 PD patients participated in this study; 152 idiopathic PD patients, 139 mGBA, 48 sGBA and 16 GD-PD. Groups were similar in age, sex, years of education and age of onset. Both sGBA and GD-PD had higher Unified Parkinson Disease Rating Scale (UPDRS) scores (p = 0.041), higher frequencies of REM sleep behavior disorder (RBD) (p = 0.022) and hallucinations (p < 0.0001) compared to the other groups of patients. sGBA experienced more non-motor symptoms (p < 0.0001), depression (p < 0.001) and worse hyposmia (p = 0.010). Trail making test was significantly longer in GD-PD followed by sGBA, mGBA and iPD (p = 0.005).

Discussion: Motor, cognitive, olfactory and psychiatric symptoms are more severe in sGBA and GD-PD compared to mGBA and iPD, reinforcing the notion that the severity of the PD phenotype is related to the severity of the mutation in the GBA gene.

Keywords: GBA; Parkinson's disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Cohort Studies
  • Female
  • Gaucher Disease / complications*
  • Gaucher Disease / genetics
  • Genetic Association Studies
  • Glucosylceramidase / genetics*
  • Humans
  • Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 / genetics
  • Male
  • Middle Aged
  • Mutation / genetics*
  • Olfaction Disorders / etiology
  • Olfaction Disorders / genetics
  • Parkinson Disease / complications*
  • Parkinson Disease / genetics*
  • Phenotype
  • REM Sleep Behavior Disorder / etiology
  • Severity of Illness Index


  • Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
  • GBA protein, human
  • Glucosylceramidase